Category: surgical glue

Medical glues are either biologically-based, cyanoacrylate, or other synthetic. The bulk of global sales of medical glues are biologically-based, (includes fibrin, thrombogen, and others), cyanoacrylate-based glues, and other synthetic glues.

Cyanoacrylate-based glues, include those from Ethicon, Adhezion Biomedical, B. Braun, Meyer-Haake, and others. Cyanoacrylates provide strong adhesion, but biologically-based glues have found more applications, both topically and internally. “Other” glues are of a variety of synthetic types; these glues have yet to gain more than 4% share globally.

Below is illustrated the growth of biologically-based glues by region, showing that most growth in this segment will be from Asia/Pacific markets, which are consistently demonstrating higher growth than in western markets.

Here are six key trends we see in the global market next in surgical sealants, glues, and hemostats:

Aggressive development of products (including by universities, startups, established competitors), regulatory approvals, and new product introductions continues in the U.S., Europe, and Asia/Pacific (mostly Japan, Korea) to satisfy the growing volume of surgical procedures globally.

Rapid adoption of sealants, glues, hemostats in China will drive much of the global market for these products, but other nations in the region are also big consumers, with more of the potential caseload already tapped than the rising economic China giant. Japan is a big developer and user of wound product consumer. Per capital demand is also higher in some countries like Japan.

Flattening markets in the U.S. and Europe (where home-based manufacturers are looking more at emerging markets), with Europe in particular focused intently on lowering healthcare costs.

The M&A, and deal-making that has taken place over the past few years (Bristol-Myers Squibb, The Medicines Company, Cohera Medical, Medafor, CR Bard, Tenaxis, Mallinckrodt, Xcede Technologies, etc.) will continue as market penetration turns to consolidation.

Growing development on two fronts: (1) clinical specialty and/or application specific product formulation, and (2) all purpose products that provide faster sealing, hemostasis, or closure for general wound applications for internal and external use.

Bioglues already hold the lead in global medical glue sales, and more are being developed, but there are also numerous biologically-inspired, though not -derived, glues in the starting blocks that will displace bioglue shares. Nanotech also has its tiny fingers in this pie, as well.

Market shares for sales of sealants, glues, and hemostats vary considerably from region to region globally due to the significant variations in the local market demand, rate of adoption of specific manufacturers’ products, the regulatory climate, local economies, and other factors. Consequently, manufacturers with significant share of sales in the U.S. or Europe or Asia/Pacific may have considerably lower or higher shares in other regions.

In the U.S., Ethicon and Baxter have dominant positions in sales of surgical sealants. However, in Europe and Asia/Pacific, Baxter has substantially smaller position, particularly relative to competitors like Takeda Pharmaceuticals and The Medicines Company.

In the market for hemostats, similarly, Ethicon and Baxter have dominant position in the U.S. market, but in Asia/Pacific and Europe, Baxter is subordinate to Takeda Pharmaceuticals, CryoLife, and others.

Proliferation of graphene applications

The nature of graphene’s structure and its resulting traits are responsible for a tremendous burst of research focused on applications.

Find cancer cells. Research at the University of Illinois at Chicago showed that interfacing brain cells on the surface of a graphene sheet allows the ability to differentiate a single hyperactive cancerous cell from a normal cell. This represents a noninvasive technique for the early detection of cancer.

Graphene sheets capture cells efficiently. In research similar to that U. Illinois, modification of the graphene sheet by mild heating enables annealing of specific targets/analytes on the sheet which then can be tested. This, too, offers noninvasive diagnostics.

Contact lens coated with graphene. While the value of the development is yet to be seen, researchers in Korea have learned that contact lenses coated with graphene are able to shield wearers’ eyes from electromagnetic radiation and dehydration.

Cheaply mass-producing graphene using soybeans. A real hurdle to graphene’s widespread use in a variety of applications is the cost to mass produce it, but Australia’s CSIRO has shown that an ambient air process to produce graphene from soybean oil, which is likely to accelerate graphenes’ development for commercial use.

Materials

Advanced materials development teams globally are spinning out new materials that have highly specialized features, with the ability to be manufactured under tight control.

3D manufacturing leads to highly complex, bio-like materials. With applications across many industries using “any material that can be crushed into nanoparticles”, University of Washington research has demonstrated the ability to 3D engineer complex structures, including for use as biological scaffolds.

Hydrogels and woven fiber fabric. Hokkaido University researchers have produced woven polyampholyte (PA) gels reinforced with glass fiber. Materials made this way have the structural and dynamic features to make them amenable for use in artificial ligaments and tendons.

Sound-shaping metamaterial. Research teams at the Universities of Sussex and Bristol have developed acoustic metamaterials capable of creating shaped sound waves, a development that will have a potentially big impact on medical imaging.

Organ-on-a-chip

In vitro testing models that more accurately reflect biological systems for drug testing and development will facilitate clinical diagnostics and clinical research.

Stem cells derived neuronal networks grown on a chip. Scientists at the University of Bern have developed an in vitro stem cell-based bioassay grown on multi-electrode arrays capable of detecting the biological activity of Clostridium botulinum neurotoxins.

Used for mimicking heart’s biomechanical properties. At Vanderbilt University, scientists have developed an organ-on-a-chip configuration that mimics the heart’s biomechanical properties. This will enable drug testing to gauge impact on heart function.

Used for offering insights on premature aging, vascular disease. Brigham and Women’s Hospital has developed organ-on-a-chip model designed to study progeria (Hutchinson-Gilford progeria syndrome), which primarily affects vascular cells, making this an affective method for the first time to simultaneously study vascular diseases and aging.

Today’s surgeon has a broad range of products from which to choose for closing and sealing wounds. These include sutures, stapling devices, vascular clips, ligatures, and thermal devices, as well as a wide range of topical hemostats, surgicalsealants and glues.

However, surgeons still primarily use sutures for wound closure and securement—sutures are cheap, familiar and work most of the time. Now, in addition to reaching for a stapling device, the surgeon must frequently decide at what point to augment or replace the commonly used items in favor of other products, which product is best for what procedure or condition, how much to use, and ease of use in order to achieve optimal patient outcomes. Because of budget pressures, the surgeon must also consider price when selecting a product. Of course in the USA, the product must also be FDA-approved, although the surgeon still has the choice of using a product off-label.

In the areas of sealants, hemostats and glues, there is room for both improvement and additional products. There are a number of products already on the market, but the fact is that there is no one product that meets all needs in all situations and procedures. There are few products that stand out from the rest, apart, perhaps, from DermaBond® and BioGlue®. There are unmet needs, and companies having the necessary technology, or which may acquire and further develop the technology, can enter this market and launch novel items. These products have yet to significantly tap the potential for wound management and medical/surgical procedures.

Fibrin sealants are used in the US in a wide array of applications; they are used the most in orthopedic surgeries, where the penetration rate is thought to be 25-30%. Fibrin sealants can, however, be ineffective under wet surgical conditions. The penetration rate in other surgeries is estimated to be about 10-15%.

Fibrin-based sealants were originally made with bovine components. These components were judged to increase the risk of developing bovine spongiform encephalopathy (BSE), so second-generation commercial fibrin sealants (CSF) avoided bovine-derived materials. The antifibrinolytic tranexamic acid (TXA) was used instead of bovine aprotinin. Later, the TXA was removed, again due to safety issues. Today, Ethicon’s (JNJ) Evicel is an example of this product, which Ethicon says is the only all human, aprotinin free, fibrin sealant indicated for general hemostasis. Market growth in the Sealants sector is driven by the need for improved biocompatibility and stronger sealing ability—in other words, meeting the still-unsatisfied needs of physician end-users.

High Strength Medical Glues

Similar to that of sealants, the current market penetration of glues in the US is about 25% of eligible surgeries. There are several strong points in favor of the use of medical glues: their use can significantly reduce healthcare costs, for example by reducing time in the surgical suite, reducing the risk of a bleed, which may mean a return trip to the OR, and general ease of use. Patients seem to prefer the glues over receiving sutures for external wound closure, as glues can provide a suture-free method of closing wounds. In addition, if glues are selected over sutures, the physician can avoid the need (and cost) of administering local anesthesia to the wound site.

Hemostats

Hemostats are normally used in surgical procedures only when conventional methics to stop bleeding are ineffective or impractical. The hemostat market offers opportunities as customers seek products that better meet their needs. Above and beyond having hemostatic agents that are effective and reliable, additional improvements that they wish to see in hemostat products include: laparoscopy-friendly; work regardless of whether the patient is on anticoagulants or not; easy to prepare and store, with a long shelf life; antimicrobial; transparent so that the surgeon continues to have a clear field of view; and non-toxic; i.e. preferably not made from human or animal materials.

Drawn from, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.”Report #S290.

In past posts, we have reported on multiple naturally-occurring substances or methods for strong adhesion that are being investigated for their potential to be exploited for medical or surgical adhesion. These include adhesives from remora, mussels, geckos, crab shells, barnacles, Australian burrowing frogs, spider webs, porcupine quills, sandcastle worms, etc.

Researchers from MedUni Vienna and Vienna University of Technology are now investigating 300 different ticks for the “cement” used by the parasites to attach to hosts. The goal is to study the composition of the natural tick “dowel” used by the mouthparts of ticks and determine how it might serve as a template for new tissue adhesives.

The Vienna research also notes other natural adhesives are similarly being investigated for medical and surgical use:

Other potential “adhesive donors” are sea cucumbers, which shoot sticky threads out of their sac; species of salamander, which secrete extremely fast-drying adhesive out of skin glands, if attacked; or insect larvae, which produce tentacles or crabs, which can remain firmly “stuck,” even under water.

The incentive for studying natural adhesives is that they have been driven by evolution to provide strong adhesion without toxicity in various wet or dry conditions that are challenging for existing synthetic or existing natural glues (e.g., fibrin glues, cyanoacrylates, etc.). Surgical glues currently in use have some limitation arising from lesser strength, ease of use, toxicity, and other shortcomings. New glues will gain wider adoption, capturing procedure volume used with sutures, clips and other closure methods, particularly in internal use, if they are stronger and/or provide tighter seals (without needing to be combined with sutures on the same incision/wound) and do not cause the toxicity that some high strength medical glues do (e.g., synthetics like cyanoacrylates; “super glues”). The biologically-derived glues (or the surfaces structures of gecko feet) avoid the toxicities of synthetics and have often proven to have very high tensile strength. (The fast-curing cement used by barnacles has been shown to have a remarkable tensile strength of 5,000 pounds per square inch.)

The bulk of medical/surgical glues are biologically-based, and soon the bulk of medical glue sales will come from Asia/Pacific.

The two graphs below show the changes in regional shares in biologically-based glues. It can be seen that from 2015 to 2022, the US and Asia-Pacific will practically switch places in terms of revenue share per region. This significant change will come about because of the intensive and enormous healthcare modernization taking place in the PRC. In 2012, the Chinese government announced its 12th five-year plan which includes the construction of 20,000 new hospital and healthcare facilities.

Source: Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World (Report #S290).

High strength medical and surgical glues currently command a $1.2 billion market that will grow to $1.7 billion by 2022, representing a 6.4% compound annual growth rate. More importantly, however, is that during this time frame the market will undergo steady shifts, including the regional representation, with growth slowing in western markets relative to Asia-Pacific and the rest of the world.

Below is illustrated the size versus growth of high strength glues in the U.S., Western Europe, Asia-Pacific and Rest of World.

Sales of sealants, glues, and hemostats projected to 2022 for the U.S. and Asia/Pacific. While these products have had tremendous success in Japan, their sales in the rest of Asia/Pacific have not yet caught up to Japan, let alone to the U.S.

But that is expected to change as the most significant growth in these markets will indeed be coming from China, Korea, Australia, India, and elsewhere in these emerging markets.

Sales of Sealants, Glues, and Hemostats in theU.S. and Asia/Pacific Markets, 2015-2022

Note: For direct comparative purposes, sales in these markets are shown on the same vertical scale.

There are several different classes of surgical sealants, glues and hemostatic products used to prevent or stop bleeding, or to close a wound or reinforce a suture line. These include fibrin sealants, surgical sealants, mechanical hemostats, active hemostats, flowable hemostats, and glues. Both sealants and medical glues are increasingly used either as an adjunct to sutures or to replace sutures.

Medical Sealants

Fibrin sealants are made of a combination of thrombin and fibrinogen. These sealants may be sprayed on the bleeding surface, or applied using a patch. Surgical sealants might be made of glutaraldehyde and bovine serum albumin, polyethylene glycol polymers, and cyanoacrylates.

Sealants are most often used to stop bleeding over a large area. If the surgeon wishes to fasten down a flap without using sutures, or in addition to using sutures, then the product used is usually a medical glue.

Hemostatic Products

The surgeon and the perioperative nurse have a variety of hemostats from which to choose, as they are not all alike in their applications and efficacy. Selection of the most appropriate hemostat requires training and experience, and can affect the clinical outcome, as well as decrease treatment costs. Some of the factors that enter into the decision-making process include the size of the wound, the amount of hemorrhaging, potential adverse effects, whether the procedure is MIS or open surgery, and others.

Active hemostats contain thrombin products which may be derived from several sources, such as bovine pooled plasma purification, human pooled plasma purification, or through human recombinant manufacturing processes. Flowable-type hemostats are made of a granular bovine or porcine gelatin that is combined with saline or reconstituted thrombin, forming a flowable putty that may be applied to the bleeding area. Mechanical hemostats, such as absorbable gelatin sponge, collagen, cellulose, or polysaccharide-based hemostats applied as sponges, fleeces, bandages, or microspheres, are not included in this analysis.

Medical Glues

Sealants and glues are terms which are often used interchangeably, which can be confusing. In this report, a medical glue is defined as a product used to bond two surfaces together securely. Surgeons are increasingly reaching for medical glues to either help secure a suture line, or to replace sutures entirely in the repair of soft tissues. Medical glues are also utilized in repairing bone fractures, especially for highly comminuted fractures that often involve many small fragments. This helps to spread out the force-bearing surface, rather than focusing weight-bearing on spots where a pin has been inserted.

Thus, the surgeon has a fairly wide array of products from which to choose. The choice of which surgical hemostat or sealant to use depends on several factors, including the procedure being conducted, the type of bleeding, severity of the hemorrhage, the surgeon’s experience with the products, the surgeon’s preference, the price of the product and availability at the time of surgery. For example, a product which has a long shelf life and does not require refrigeration or other special storage, and which requires no special preparation, usually holds advantages over a product which must be mixed before use, or held in a refrigerator during storage, then allowed to warm up to room temperature before use.